The present invention relates to novel substituted sulfonylquinolines useful as pharmaceutical agents, to methods for their production, to pharmaceutical compositions which include these compounds and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment. The novel compounds of the present invention are neuropeptide Y antagonists useful for the treatment of obesity and hypertension.
Neuropeptide Y (NPY) is involved in the control of feeding in mammals. Administration of neuropeptide Y into the central nervous system causes a dramatic increase in feeding in rats and based on the activity of fragments of the NPY molecule, this effect appears to be mediated by the Y.sub.1 subtype of NPY receptor (Dryden S., Frankish H., Wang Q., and Williams G. Neuropeptide Y and energy balance: one way ahead for the treatment of obesity? Eur. J. Clin. Invest., 1994;24:293-308). The compounds of the present invention are neuropeptide Y.sub.1 antagonists and are useful in the treatment of obesity.
Neuropeptide Y is also involved in the regulation of blood pressure. Neuropeptide Y antagonists have been shown to be effective antihypertensive agents (Edvinsson L., Hakanson R., Wahlestedt C., and Uddman R. Effects of Neuropeptide Y on the cardiovascular system. Trends Pharmacol. Sci., 1987;8:231-235). The compounds of the present invention are neuropeptide Y antagonists and are useful in the treatment of hypertension.
We have surprisingly and unexpectedly found that a series of sulfonylquinolines are neuropeptide Y antagonists which bind selectively to the neuropeptide Y.sub.1 receptor subtype and are thus useful as antiobesity and antihypertensive agents.